TB meningitis (TBM) is a devastating illness with high risk of mortality and severe neurologic morbidity predominantly affecting young children. The best regimen and optimal drug doses for treatment of pediatric TBM in children are unknown, as only one clinical trial of pediatric TBM treatment has ever been conducted. In two recent clinical trials in adults with TBM, higher-dose rifampin given IV early in treatment or an oral fluoroquinolone given daily for 8 weeks significantly reduced mortality and severe disability. It i unclear whether these strategies may improve outcomes in children, as the disease spectrum is different -- lower mortality and added risk of neurodevelopmental morbidity -- and the doses needed to achieve adult targets associated with improved outcomes have not been proven. Recently, the World Health Organization recommended an increase in the doses of first-line TB drugs, including isoniazid (H) and rifampin (R), for children, recognizing that previously-recommended doses were often sub-therapeutic, but the dose of rifampin (R), the drug that drives treatment response in TB, is likely still too low for TBM. Ethambutol (E), recommended as a fourth drug in TBM regimens (with H, R, and pyrazinamide (Z)), has poor penetration into cerebrospinal fluid (CSF) and may be less effective than levofloxacin (L), a widely-available oral drug with excellent CSF penetration, proven activity against Mycobacterium tuberculosis, and recent promising safety and PK data from children receiving it for latent or active multidrug-resistant TB. The goal of this proposal is to evaluate the pharmacokinetics (PK), safety, and treatment outcomes among children with TBM receiving higher-dose IV R given early in treatment with or without L for eight weeks as part of multidrug treatment for TBM. Children ages 6 months to 8 years with TBM will be recruited through Byramji Jeejeebhoy Government Medical College in Pune, India; the National Institute for Research in TB and collaborating clinical sites (Institute of Child Health and the Kanchi Kamakoti CHILDS Trust Hospital) in Chennai, India; and the Malawi- Liverpool-Wellcome Trust Clinical Research Programme site in Blantyre, Malawi. For the intensive phase of TB treatment (first 8 weeks), 120 participants will be randomized 1:1:1 to receive standard dose HRZE for 8 weeks (control arm), HRivZE (IV R substituted for oral R for two weeks, with optimal IV R dose estimated using modeling of existing PK data from children and PK/pharmacodynamic data from adults with TBM), or HRivZL (R IV for two weeks plus levofloxacin at a dose of 20 mg/kg daily substituted for ethambutol for 8 weeks). Plasma and sparse CSF sampling will be performed, and plasma and CSF PK for H, R, and L will be determined. Treatment-effect relationships will be explored using a graded outcome measure (death/severe neurologic disability, moderate disability, mild disability, or no neurologic disability) and neurocognitive testing. Specimens will be biobanked for future biomarker studies. This trial will yield critically important data to inform drug selection and dosing strategies for children with TBM and will be applicable to children with TBM globally.